A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid–liquid phase separation to promote oncogenic YAP signaling
| Autor: | Zuo-zhen Yang, Tian Tian, Aifu Lin, Liangjing Wang, Rui-hua Li, Ya-Zhuo Liu, Wenqi Wang, Chengyu Shi, Yan Xiong, Xin-Yu He, Xu Li, Zhen Zhang, Jian Liu, Tianhua Zhou, Qingfeng Yan, Ling-jie Sang, Fang-zhou Liu, Qiwei Ge, Huai-Qiang Ju, Jian-Zhong Shao, Jun-Hong Li |
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| Rok vydání: | 2021 |
| Předmět: |
Cell signaling
Clinical Sciences Phosphatidic Acids Protein Serine-Threonine Kinases Biology Article Cell Line Cell Line Tumor Breast Cancer Genetics 2.1 Biological and endogenous factors Humans Hippo Signaling Pathway Aetiology Small nucleolar RNA Molecular Biology Tissue homeostasis Cancer Biological Phenomena Cell Proliferation Hippo signaling pathway Tumor Kinase Phosphatidic acid binding YAP-Signaling Proteins Cell Biology Phosphoproteins Cell biology RNA Phosphorylation Long Noncoding RNA Long Noncoding Biochemistry and Cell Biology Signal transduction Biotechnology Developmental Biology Signal Transduction |
| Zdroj: | Cell Res Cell research, vol 31, iss 10 |
| ISSN: | 1748-7838 1001-0602 |
| Popis: | Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1). |
| Databáze: | OpenAIRE |
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